TY - JOUR T1 - Multiscale Imaging Reveals Aberrant Functional Connectome Organization and Elevated Dorsal Striatal <em>Arc</em> Expression in Advanced Age JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0047-19.2019 VL - 6 IS - 6 SP - ENEURO.0047-19.2019 AU - Luis M. Colon-Perez AU - Sean M. Turner AU - Katelyn N. Lubke AU - Marjory Pompilus AU - Marcelo Febo AU - Sara N. Burke Y1 - 2019/11/01 UR - http://www.eneuro.org/content/6/6/ENEURO.0047-19.2019.abstract N2 - The functional connectome reflects a network architecture enabling adaptive behavior that becomes vulnerable in advanced age. The cellular mechanisms that contribute to altered functional connectivity in old age, however, are not known. Here we used a multiscale imaging approach to link age-related changes in the functional connectome to altered expression of the activity-dependent immediate-early gene Arc as a function of training to multitask on a working memory (WM)/biconditional association task (BAT). Resting-state fMRI data were collected from young and aged rats longitudinally at three different timepoints during cognitive training. After imaging, rats performed the WM/BAT and were immediately sacrificed to examine expression levels of Arc during task performance. Aged behaviorally impaired, but not young, rats had a subnetwork of increased connectivity between the anterior cingulate cortex (ACC) and dorsal striatum (DS) that was correlated with the use of a suboptimal response-based strategy during cognitive testing. Moreover, while young rats had stable rich-club organization across three scanning sessions, the rich-club organization of old rats increased with cognitive training. In a control group of young and aged rats that were longitudinally scanned at similar time intervals, but without cognitive training, ACC–DS connectivity and rich-club organization did not change between scans in either age group. These findings suggest that aberrant large-scale functional connectivity in aged animals is associated with altered cellular activity patterns within individual brain regions. ER -